Ab initio quantum mechanical calculations of pKas of isolated molecules and molecules undergoing chemical reactions: pKa of acetic acid during α-proton abstraction

Abstract

Aqueous-phase proton affinities (PA(aq)) were calculated for 14 carboxylic acids, 15 amines, and 16 alcohols using abinitio quantum mechanically calculated gas phase proton affinities (PA(gas), MP2/6-31+G**//HF/6-31+G**) and relative solvation energies of the acid and its conjugate base (ΔΔG_solv, IPCM-HF/6-31+G**) calculated with the isodensity surface-polarised continuum model (PA(aq)=PA(gas)+ΔΔG_solv). After empirical linear scaling the correlation coefficients (r²) between the calculated and experimental pK_as were 0.94–0.98 for the three groups of molecules. Carboxylic acids, amines and alcohols have different correlation equations indicating systematic errors in the calculated energies for molecules with different acidic groups. The linear equation for carboxylic acids was used to estimate the change in the pK_a of the carboxyl group of acetic acid from the calculated 4.8 (pK_a(exp)=4.6) of the reactant, acetic acid, to 13.3 of the product, enolate of carboxylic acid, during α-proton abstraction by methoxide. It was shown that the calculated PA(aq) values can be used to estimate pK_as of isolated molecules and molecules undergoing chemical reactions.